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研究生： 林鈺翔
Yushiang Lin
論文名稱： 利用鈀金屬催化甲酸還原反應不對稱合成天然物 Zoapatanol 前驅物
Apply the method of regioselective palladium-catalyzed formate reduction to synthesize Zoapatanol precursor.
指導教授： 侯敦仁
Duen-Ren Hou
口試委員:
學位類別： 碩士
Master
系所名稱： 理學院 - 化學學系
Department of Chemistry
畢業學年度： 97
語文別： 中文
論文頁數： 150
中文關鍵詞： 鈀金屬催化甲酸還原反應
外文關鍵詞： Zoapatanol
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    • 本論文的研究主題是將「環閉合置換反應（ring-closing metathesis , RCM）後產生之烯烴進行具位置選擇性衍生化的方法」，藉由鈀金屬催化甲酸還原反應(palladium-catalyzed formate reduction)來達成此目的。我們使用含氧原子的七圓雜環化合物 4 為模型，以改變甲酸還原反應中磷配位基的方式，找出適用含氧七圓雜環產生環外烯的最佳條件。
    為了探討此系統對於有機合成上得實用性，我們以Cossy教授合成天然物Zoapatanol時，合成路徑中的中間物化合物 C5為目標產物。Zoapatanol的主體架構為含有兩個掌性中心的含氧七圓雜環，而第一個掌性中心的建構是利用Sharpless進行不對稱氧化來得到，第二個掌性中心則是以Felkin-Anh model來建構出第二個掌性中心。

    The method for regioselective palladium-catalyzed formate reduction of allylic acetates formed by ring closing metathesis was developed. We used ((E)-2,5,6,7-tetrahydro-7-methyl-7-phenyloxepin-3-yl)methyl acetate 4 as the model compound, and found an optimized condition for the formate reduction by screening several ligand.
    In order to apply this methodology to organic synthesis , We planned to synthesize compound C5 , that was the key synthetic intermediate in Cossy’s synthesis to product Zoapatanol . Zoapatanol contains a seven membered oxygen-heterocycle with two chiral centers. The first chiral center was prepared utilizing the Sharpless asymmetric oxidation, and the second chiral center was built by Grignard reaction whose stereochemistry assume to follow the Felkin-Anh model.

    總 目 錄 中文摘要……………………………………………І Abstract…………………………………………………………………Ⅱ 誌謝…………………………………………………………….…………. ІІІ 總目錄……………………………………………………………………ІV 圖目錄…………………………………………………………………VI 表目錄…………………………………………………………………VІІI 附圖目錄……………………………………………………………….IX 第一章 序論……………………………………………………………...... 1 1-1 前言…………………………………………… .........................1 1-2 烯烴置換反應與環閉合置換反應的介紹…………………………..6 1-3 鈀金屬催化甲酸還原反應的介紹………………………………....13 第二章 鈀金屬催化甲酸還原反應應用於環化合物的研究與討論.........17 2-1 「模型」(model)的設計………………………………………….. 17 2-2 環外烯烴化合物5逆合成分析………………………………..... ..18 2-3 起始物 1 的製備……………………………………………....... ..18 2-4 起始物 2 的製備.........………………………………………….....19 2-5 起始物 4 的製備……………………………………………......... 20 2-6 化合物4進行鈀金屬催化甲酸還原反應的機制………..........…. 21 2-7 串連環閉合置換反應與利用鈀金屬催化甲酸還原反應應用於「模型」之結論………………………………………………………..........24 第三章 合成上的應用…………………………………… …................. ..25 3-1 合成分子的選定………………………………… … ......................25 3-2 天然物 Zoapatanol 介紹……………………… …........................ 26 3-3 設計目標產物 19………………………… …................................ 31 第四章 將RCM與鈀金屬催化甲酸還原反應串連的系統應用於合成天然物 Zoapatanol 前驅物之研究與討論…………………...........32 4-1 目標產物 19 的合成構思………………………………................32 4-2 文獻中Felkin-Anh model 的實例……………………………........33 4-3 A 區塊(block)合成…………………................................................34 4-4 B 區塊(block)合成……………………............................................36 4-5 B 區塊(block)化合物製備成Grignard 試劑與A 區塊(block)反應的 測試與結果…………………………………......................................... 37 4-6 Williamson醚化反應的測試與結果…………………………….....40 4-7 Williamson醚化反應的測試結論………………………………......50 4-8 修改設計路徑………………………………………………............50 4-9 環閉合置換反應雙鍵轉移的測試…………………………............51 4-10重新設計A區塊的合成路徑……………………………..............52 第五章 總結………………………………………………….....................54 第六章 實驗………………………………………………….....................55 6-1 溶媒及處理過程................................................................................55 6-2 實驗器材與儀器................................................................................55 6-3 實驗步驟............................................................................................56 第七章 參考文獻………………………………………………………….85

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